Maze Lab

Laboratory of Mechanistic Neuroepigenetics and Disease

Research

The Maze laboratory is focused on understanding the complex interplay between chromatin regulatory mechanisms in brain and neuronal plasticity. We combine a wide variety of biochemical, biophysical, molecular and behavioral approaches to assess the role of histone proteins, and their associated posttranslational modifications, turnover dynamics and remodeling activities, in the regulation of normal neurodevelopment, and the contribution of such processes, or aberrations thereof, to neurological and psychiatric disease. We place particular emphasis on psychiatric disorders associated with monoaminergic (e.g., serotonin, dopamine, etc.) dysfunction, such as major depressive disorder and drug addiction, as well as neurodevelopmental syndromes resulting in deficits in synaptic plasticity and intellectual disability (e.g., Down syndrome and autism). Being both ‘basic’ and translational in nature, our work – so-called “mechanistic neuroepigenetics” – employs state-of-the-art gene and chromatin arraying technologies, analytical chemistry (e.g., mass spectrometry and 14C bomb pulse labeling) and neurobiological phenotyping, in both rodents and humans (postmortem brain and iPSC derived neurons), to explore novel chromatin phenomena in the central nervous system. This includes the identification and characterization of neuronally enriched histone modifications, chromatin “readers,” “writers” and “erasers,” all of which play critical roles in neuronal plasticity and behavioral adaptation.

Featured

Ian Maze, Ph.D., 2017 One Mind Rising Star Award winner proposes a potent aim: to determine whether testing the blood for reduced levels of a serotonin-modified protein could help to predict susceptibility to depression under stress, to diagnose major depressive disorder, and/or to predict whether antidepressant medications might help specific patients. Presentation filmed at the 23rd Music Festival for Brain Health, September 16, 2017 Read More

Sasha Fulton

Andrew Stewart

Polina Safovich

Yang Lyu

Grants

Active Grants

R01 MH116900, (Maze)National Institutes of Health/NIH/DHHS (NIMH)Molecular studies of neural histone monoaminylation in normal and aberrant brain plasticity
The major goals of this project are to investigate cell-type, brain region and sex specific roles for histone monoaminylation in the precipitation of depressive-like behaviors and antidepressant actions in rodent models of major depressive disorder.

DP1 DA042078, Avenir Award (Maze)National Institutes of Health/NIH/DHHS (NIDA)Roles for histone monoaminylation in cocaine-induced transcriptional and behavioral plasticity
The major goals of this project are to understand whether dopaminergic dysfunction in rodent models of cocaine addiction impact the expression of histone dopaminylation in brain, as well as how such alterations in monoaminylation impact addictive-like phenotypes.

P50 MH096890, Conte Center (Nestler)National Institutes of Health/NIH/DHHS (NIMH)Epigenetic mechanisms in depression
The major goals of this project are to continue investigating the “epigenetic” mechanisms underlying human
major depressive disorder, as well as individual responses to antidepressants, using both rodent model systems and human postmortem tissues.
Role: Co-PI (Project 3)

Basil O’Connor Starter Scholar Research Award (Maze)March of DimesAberrant epigenetic mechanisms contributing to Down syndrome: a novel role for the histone reader protein BRWD1
The major goals of this project are to characterize the role of BRWD1 and its target genes in mediating intellectual disability in Down syndrome brain.

One Mind – Early Diagnostics Rising Star Research Award (Maze)One Mind InstituteValidation of histone serotonylation as a predictive blood biomarker for stress susceptibility, major depressive disorder and antidepressant efficacy
The overarching goal of this project is to fully test the hypothesis that newly discovered histone serotonylation may be used as a peripheral biomarker for MDD and/or antidepressant efficacy in human patients in order to aid in the implementation of more effective therapeutic interventions.

R21 DA044767, (Maze/David Shternberg)National Institutes of Health/NIH/DHHS (NIDA)Application of intein-based chemical methods to directly manipulate neuronal histone modifications in rodent models of addiction
The major goals of this project are to further develop and implement novel intein-based chemical
methodologies for directly manipulating histone and other protein modifications in vivo in brain, with an extended emphasis on applying these approaches for use in rodent addiction models.

Past Grants

Alfred P. Sloan Research Fellow in Neuroscience (Maze)Alfred P. Sloan FoundationMechanistic Neuroepigenetics
This is a career award to promote my laboratory’s advancement of the new field of mechanistic
neuroepigenetics.

MQ15FIP100011 (Maze)
MQ: Transforming Mental Health Research FellowshipWellcome TrustHistone monoaminylation in the CNS: novel insights into the cause and treatment of human depression
The major goals of this project are to understand whether serotonergic dysfunction in rodent models of human depression impact the expression of histone serotonylation in brain, as well as if current antidepressants affect such expression.

Fay/Frank Seed Grant (Maze)Brain Research FoundationBeyond neurotransmission: exploring roles for synaptic dopaminylation in drug-induced plasticity
The major goals of this project are to use novel chemical approaches to identify synaptic proteins that are dopaminylated in the context of drug abuse (specifically cocaine) for future molecular and behavioral characterizations.

NARSAD Young Investigator Award (Maze)Brain & Behavior Research FoundationEpigenomic profile and function of histone variant H3.3 dynamics in depression
The major goal of this project was to investigate the role of histone turnover/H3.3 dynamics in the mediation of
transcriptional abnormalities contributing to depressive-like behaviors in rodent models of human depression.

Rosen Family Research Scholar Award (Maze)Friedman Brain Institute Pilot Fund PartnershipFunction of a novel ‘reader’ of neuronal chromatin in Trisomy 21 associated Alzheimer’s disease
The major goals of this project are to develop a novel hiPSC derived neuronal model of Down syndrome in order
to investigate whether triplication of the neuronally enriched histone reader protein BRWD1 contributes to
observed neurological/synaptic impairments.

T32 MH087004 (Salton)National Institutes of Health/NIH/DHHS (NIMH)Genome-wide chromatin accessibility profiling in major depressive disorder reveals astrocytic specific signatures of reward processing deficits in the orbitofrontal cortex
The major goals of this training grant project are to investigate epigenetic mechanisms underlying human
major depressive disorder, with a specific emphasis on chromatin mediated glial dysfunction leading to
reward processing deficits in the frontal cortex.
Role: Predoctoral Trainee (Fulton)

Active Grants (Lab Members)

F31 DA045428 (Lepack)National Institutes of Health/NIH/DHHS (NIDA)Functions for histone dopaminylation in cocaine-induced plasticity
The major goals of this fellowship project are to understand whether dopaminergic dysfunction in rodent
models of cocaine addiction impact the expression of histone dopaminylation in brain, as well as how such
alterations in monoaminylation impact addictive-like phenotypes.

NARSAD Young Investigator Award (Farrelly)Brain & Behavior Research FoundationHistone serotonylation: a novel epigenetic mechanism mediating depressive-like phenotypes
The major goals of this young investigator award are to understand whether serotonergic dysfunction in
rodent models of human depression impact the expression of histone serotonylation in brain, as well as if
current antidepressants affect such expression.

T32 DA007135 (Devi)National Institutes of Health/NIH/DHHS (NIDA)Role of protein dopaminylation in drug addiction
The major goals of this project are to use novel chemical approaches to identify synaptic proteins that
are dopaminylated in the context of drug abuse (specifically cocaine and heroin) for future molecular
and behavioral characterizations.
Role: Postdoctoral Trainee (Bastle)

Awards

Ian Maze: 2019 Dr. Harold and Golden Laport Basic Research Award

Lorna Farrelly: The Friedman Brain Institute 2019 POSTDOC Award: for the best record of achievement in neuroscience.

Andrew Stewart: NSF Graduate Research Fellowship. It is awarded based upon an individual’s potential to “contribute to the US science and engineering enterprise.”